The dopamine transporter, localized on dopamine neurons, is an effective marker for a number of pathological states, including Parkinson's disease. Furthermore, as a principal target of cocaine in the brain, the transporter has been implicated in the addictive properties of cocaine. Imaging of the dopamine transporter in human brain is one of the most rapidly growing fields of PET and SPECT imaging research. As 99mtechnetium is technically the simplest isotope to prepare for routine brain imaging, we tested the feasibility of developing a technetium (99Tc) agent by linking chelated rhenium to analogs of WIN 35,428. Phenyltropane analogs of WIN 35,428 are ligands of choice for PET and SPECT imaging of the dopamine transporter. Within this series, O-816R (RS)-[N-(2-((3'-N'-propyl-(1"R-3" -(4-fluorophenyl)tropane-2" -carbomethoxy))(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato]rhenium (V)oxide) was the most potent drug at the dopamine transporter (IC50 5.99 q 0.81 nM; n = 7) and was 20-, 6,700- fold selective for the dopamine vs serotonin or norepinephrine transporters, respectively. The compound was labeled with 99mTc to observe whether technepine crosses the blood-brain barrier to accumulate in striatum. Two adult rhesus monkeys were administered 99mTc-technepine intravenously and brain images were acquired for 3 h. Coronal, sagittal and rotating three-dimensional displays were calculated from the data and magnetic resonance imaging (MRI) scans on the same monkeys were acquired to develop neuroanatomical correlates. SPECT imaging revealed that technepine crossed the blood-brain barrier and localized in the striatum. Technepine is the first reported technetium-labeled compound to cross the blood-brain barrier and accumulate in a selective target in brain. This study demonstrates the feasibility of developing technetium-labeled compounds